Medication adherence rates among youth living with HIV are inadequate to effectively manage the disease, and novel interventions grounded in basic behavioral sciences are needed. Emerging evidence suggests that prospective memory (PM) could represent an important piece of the puzzle. PM is defined as the neurocognitive capacity to successfully form, maintain, and execute an intention at a particular point in the future in response to a specific cue. In response to PA-11-063, this proposal plans to translate basic cognitive neuroscience regarding PM into a more potent adherence intervention for YLH, a population at high risk for poor cognitive function, substance abuse, and poor adherence. While text message reminders are an increasingly popular adherence support, evidence of efficacy is equivocal particularly for the maintenance of adherence after reminders end. By using basic cognitive neuroscience to enhance the potency of technology- based interventions to improve PM for adherence tasks, we hope to achieve both greater initial gains as well as sustained improvements in adherence for youth with and without substance abuse. Although a larger trial is necessary to determine if substance abuse will moderate the effects of the intervention, the goal of this proposal is to develop a potent adherence intervention that can be used universally in this high-risk population. PA-11-063 specifies three phases of intervention development: 1) defining intervention target; 2) characterizing intervention effects; 3) assessing feasibility and refinement. In Phase 1, we will conduct theory-driven laboratory studies to improve three components of PM using a within-subjects design and traditional cognitive neuroscience tasks (strategic encoding, monitoring, and cue salience) in 60 youth from clinics where the co- PIs are based (San Diego and Detroit). In Phase 2, we will translate promising Phase 1 PM interventions to the youth's natural context to target adherence by combining them text messaging, and test for signals of efficacy using a multiple baseline design for YLH with suboptimal adherence (N=24; 12 with substance abuse and 12 without). In Phase 3, we will conduct a pilot randomized clinical trial comparing the technology-based PM adherence intervention to text message reminders (N=60).